Back in 1944, physicist Erwin Schrödinger’s masterpiece, What Is Life? , provided the world with a cue about the basic tenets of life. In subsequent decades, discoveries advanced our knowledge on the complexities of life, on how cells function and propagate. From single cell bacteria to complex multi-cellular organisms like humans, cells remain at the heart of all functions. A landmark discovery in 2016 now takes our understanding a step forward in identifying a minimal set of instructions required for a cell to exist and self-propagate. With this, synthetic biology has become a serious contender to other forces for an understanding of the origin of life on earth.
It is a story of biologist J. Craig Venter and his 15-year-old journey in the quest towards creating an artificial cell. A milestone was achieved this year when his team reported the creation of a bacterial cell, Mycoplasma, with a minimal genome built with the help of man-made machines. They called it JCVI-syn3.0, containing 5,31,560 base pairs and just 473 genes. Compare this with the common gut bacteria, E. coli, that has nearly 5,000 genes. This was the smallest artificial genome ever created. Transplanting it into a living cell, which has its own genome lost during the process, made it the first viable, self-propagating cell, one that did not exist in nature before.
Mycoplasma is an ideal organism to work with in synthetic biology as it contains some of the smallest and parsimonious genomes in the bacterial kingdom and is devoid of a cell wall. A smaller genome is easier to synthesise and the lack of a cell wall makes the bugs easier to manipulate and receive foreign DNA. First, Dr. Venter’s team discovered the minimum number of genes required for Mycoplasma mycoides to survive and propagate by using a method called global transposon mutagenesis. Subsequently, they created JCVI-syn3.0 in three steps: design, build and test. In the first step, with the help of computers, the sequences of genes and other markers were designed from scratch. In addition to the 473 minimal genes, the JCVI-2yn3.0 genome also contained some artificial DNA sequence as markers. These markers are the codes for the names of all the scientists who worked in the project, a website address for the organism and an email ID. The build stage included synthesising individual genes and the marker elements and cloning them in yeast that can produce viable large DNA segments (bacteria can’t replicate long pieces of DNA). The final test phase included transplanting the synthetic genome into a recipient cell of a different species, Mycoplasma capricolum .
Although the scientific research underlying JCVI-syn3.0 has been hailed as one of the landmark discoveries of the year 2016, it has not augured well among some, especially those who believe that life can only be created and destroyed by god. Can creating a minimal genome and inserting that into a recipient cell claim to make a new life and are scientists trying to play god by attempting to create cells from scratch? The answers to both are a resounding “no”. First of all, JCVI-syn3.0 is not a synthetic form of life but a synthetic genome inserted into a naturally occurring cell. The work paves the way to create cells from scratch in the future but at best, JCVI-syn3.0 is part synthetic. Second, despite the social and ethical concerns behind such work — and many of those are genuine that can be addressed by putting stringent regulatory and legal framework — a discovery of a true synthetic cell has positive implications especially for India. In addition to improving our fundamental understanding on how cells grow and divide, creation of self-replicating artificial synthetic cells, when achieved, will have far-reaching applications in environment, health and agriculture. For example, India has a growing urban waste problem and many of her rivers and lakes are polluted with human excreta and with toxic industrial effluent. Synthetic bugs can be created from scratch to produce enzymes and chemicals that can chew up or degrade plastic in urban waste, digest toxic and destroy unwanted material in rivers and lakes.
In the health sector, creating artificial cells with immobilised or insoluble hemoglobin can provide effective solutions as oxygen carriers, which can be engineered to bear genes of interest providing boost in immunity and disease resistance. Similarly in agriculture, synthetic cells can help us understand how to make crops resistant against drought and pests and at the same time providing with additional nutrition. Coupled with our knowledge on artificial intelligence, human longevity and gene editing, synthetic biology with its versatile tools has potential to solve many problems of our society.
To end, perhaps the most compelling reason to get excited about synthetic cells comes from what physicist Richard Feynman once said: “What I cannot create, I don’t understand”. No wonder the JCVI-syn3.0 is coded for the same quote in its genome and promises to live up to Feynman’s prophecy.
Binay Panda is at Ganit Labs, Bengaluru.